Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials.


Journal

Vaccine
ISSN: 1873-2518
Titre abrégé: Vaccine
Pays: Netherlands
ID NLM: 8406899

Informations de publication

Date de publication:
24 04 2019
Historique:
received: 15 11 2018
revised: 14 03 2019
accepted: 20 03 2019
pubmed: 3 4 2019
medline: 17 9 2020
entrez: 3 4 2019
Statut: ppublish

Résumé

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies. Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period. Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race. No safety concerns arose, supporting the favorable benefit-risk profile of RZV.

Sections du résumé

BACKGROUND
The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.
METHODS
Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30 days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12 months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.
RESULTS
Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.
CONCLUSIONS
No safety concerns arose, supporting the favorable benefit-risk profile of RZV.

Identifiants

pubmed: 30935742
pii: S0264-410X(19)30377-9
doi: 10.1016/j.vaccine.2019.03.043
pii:
doi:

Substances chimiques

Adjuvants, Immunologic 0
Herpes Zoster Vaccine 0
Vaccines, Synthetic 0

Banques de données

ClinicalTrials.gov
['NCT01165177', 'NCT01165229']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2482-2493

Investigateurs

Anitta Ahonen (A)
Thiago Junquera Avelino-Silva (TJ)
Jose Fernando Barba-Gomez (JF)
Johan Berglund (J)
Carlos Brotons Cuixart (CB)
Covadonga Caso (C)
Roman Chlibek (R)
Won Suk Choi (WS)
Anthony L Cunningham (AL)
Maria Guiseppina Desole (MG)
Peter Eizenberg (P)
Meral Esen (M)
Emmanuelle Espié (E)
Pierre Gervais (P)
Wayne Ghesquiere (W)
Olivier Godeaux (O)
Iris Gorfinkel (I)
David Shu Cheong Hui (DSC)
Shinn-Jang Hwang (SJ)
Tiina Korhonen (T)
Martina Kovac (M)
Edouard Ledent (E)
Edward Leung (E)
Myron J Levin (MJ)
Silvia Narejos Perez (SN)
Jose Luiz Neto (JL)
Karlis Pauksens (K)
Airi Poder (A)
Maria Luisa Rodriguez de la Pinta (MLR)
Lars Rombo (L)
Tino F Schwarz (TF)
Jan Smetana (J)
Tommaso Staniscia (T)
Juan Carlos Tinoco (JC)
Azhar Toma (A)
Ilse Vastiau (I)
Timo Vesikari (T)
Antonio Volpi (A)
Daisuke Watanabe (D)
Lily Yin Weckx (LY)
Toufik Zahaf (T)

Informations de copyright

Copyright © 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Auteurs

Marta López-Fauqued (M)

GSK, Wavre, Belgium. Electronic address: marta.x.lopez-fauqed@gsk.com.

Laura Campora (L)

GSK, Wavre, Belgium. Electronic address: laura.e.campora@gsk.com.

Frédérique Delannois (F)

GSK, Wavre, Belgium. Electronic address: frederique.x.delannois@gsk.com.

Mohamed El Idrissi (M)

GSK, Rixensart, Belgium. Electronic address: mohamed.s.elidrissi@gsk.com.

Lidia Oostvogels (L)

GSK, Wavre, Belgium. Electronic address: cornelia.oostvogels@orange.fr.

Ferdinandus J De Looze (FJ)

AusTrials Pty Ltd, Sherwood and School of Medicine, University of Queensland, Brisbane, Queensland, Australia. Electronic address: f.delooze@trialworks.com.au.

Javier Diez-Domingo (J)

Vaccine Research Unit, Fundación para el Fomento de la Investigación Sanitaria y Biomédica, Valencia, Spain. Electronic address: jdiezdomingo@gmail.com.

Thomas C Heineman (TC)

GSK, King of Prussia, PA, USA. Electronic address: tch3768@gmail.com.

Himal Lal (H)

GSK, King of Prussia, PA, USA. Electronic address: himallal@yahoo.com.

Janet E McElhaney (JE)

Health Sciences North Research Institute, Sudbury, Ontario, Canada. Electronic address: jmcelhaney@hsnri.ca.

Shelly A McNeil (SA)

Canadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: Shelly.McNeil@nshealth.ca.

Wilfred Yeo (W)

School of Medicine, University of Wollongong, Wollongong, Australia. Electronic address: wilf@uow.edu.au.

Fernanda Tavares-Da-Silva (F)

GSK, Wavre, Belgium. Electronic address: fernanda.tavares@gsk.com.

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